This proposal is being submitted to the NIDCR PAR-05-031, "Multidisciplinary Research on Oral Manifestations Associated with HIV/AIDS". Our proposal, "Crosstalk among oral and gastrointestinal soluble innate factors, HIV and microbes" is being submitted by NYU College of Dentistry (NYUCD), with Dr. Daniel Malamud as principal investigator. Dr. Malamud has assembled a talented group of investigators for NYUCD, NYU School of Medicine (NYUSoM) and the Aaron Diamond AIDS Research Center (ADARC), all located within a few blocks of each other on First Avenue in New York City. The proposal consists of 4 interrelated research projects, an Administrative/Biostatistical Core and a Clinical Core. The entire proposal utilizes the same case controlled study population consisting of 85 HIV+, HAART naive subjects who will subsequently begin antiretroviral therapy. There will also be a similar cohort of HIV- subjects. The clinical core will obtain oral and Gl samples, monitor patient progress, carry out complete oral health examinations, and maintain all subject records. Project 1 (Dr. Linqi Zhang, ADARC) will determine the whole saliva proteome comparing HIV-, HIV+/HAART naive, and HIV+ post-HAART samples. Studies will focus on soluble molecules that are part of the host innate defense system. Project 2 (Dr Yihong Li, NYUCD) will define the oral microbiota in HIV vs. HIV+ saliva samples and HIV+ before and after HAART. Studies will focus on overall microbial diversity, and quantitation of bacteria that are altered after HIV infection, and/or related to caries and periodontal disease. Project 3 (Dr. Michael Poles, NYUSoM) will study the remainder of the Gl track using endoscopy to obtain fluid and biopsy samples. His study will focus in innate immune mediators and Gl microbes, and his data compared to Projects 1 and 2. Project 4 (Dr. Daniel Malamud, NYUCD) will study antibacterial and antiviral activities in saliva, focusing on the innate host defense system. In addition he will determine the ability to infect buccal vs. rectal tissue in vitro, and compare the HIV-1 variants obtained from oral, Gl and blood. The Administrative/Biostatistical Core (Drs. Malamud and Norman) will oversee the entire study via an Executive Committee and an External Advisory Committee. All data and statistical analyses will be handled by this core. The overall goal is to define the interactions between host defense molecules and bacteria in HIV infection and subsequent antiretroviral therapy.